Our initial results demonstrated that 2,3,7,8,-TCDD, the prototype of the class, could suppress antibody production following either subchronic exposure (14 day) or direct exposure with cultured splenocytes from untreated mice. Direct exposure produced an equivalent dose-related suppression of a variety of in vitro antibody responses requiring a differential role by accessory cells, thereby suggesting that the B-lymphocyte was the primary target. The IC50 of this suppression was about 10 nM, which suggested that it may be receptor mediated. Our results have indicated that direct exposure to either 2,3,7,8-TCDD (1-30 nM) or 3-methylcholanthrene (2-400 uM), a PAH with a strong affinity for the Ah receptor (i.e., the receptor implicated in other actions by the dioxins), produced a dose-related and equivalent suppression of the in vitro antibody response by spleen cells from both the B6C3F1 mouse (Ah+) and the DBA/2 mouse (Ah-). Previous results have indicated that 2,7-dichlorodibenzo-p-dioxin (DCDD) can neither bind to the Ah receptor nor produce the associated effects, including induction of cytochrome P1-450. Our results have indicated that direct exposure to 2,7-DCDD can suppress the in vitro antibody response and that the concentrations required to produce this suppression were similar in magnitude to 2,3,7,8-TCDD (i.e., 1-30 nM). An initial experiment with subchronic exposure (14 days) to 2,7-DCDD demonstrated a suppression of the antibody response (about 50% with 0.1 ug/kg/day) without any induction of arylhydrocarbon hydroxylase (i.e., highest dose tested was 10 ug/kg/day). In the same experiment, subchronic exposure to 2,3,7,8-TCDD at 1 ug/kg/day produced both effects. These results are significant since they indicate that the dioxin-induced suppression of the antibody response need not be associated with the Ah receptor. Thus, the preliminary results of this investigation may be the first indications for another class of dioxin receptors. From a toxicological viewpoint, these results indicate that the existing structure-activity relationship may not account for all toxicity associated with this class of chemicals, and certainly cannot account for the immunotoxicity.